NPM1 promotes nasopharyngeal carcinoma metastasis and stemness by recruiting Mdm2 to induce the ubiquitination-mediated degradation of p53.

Abstract

Nasopharyngeal carcinoma (NPC) is clinically challenging due to the development of distant metastasis following initial therapy. Therefore, it is necessary to elucidate the mechanisms underlying metastases to develop novel therapeutic strategies. Nucleophosmin 1 (NPM1) has been directly linked to the development of human tumors and may have both tumor-suppressing and oncogenic properties. Although NPM1 is often overexpressed in solid tumors of various histopathological origins, its specific function in mediating the development of NPC is still unknown. Here, we investigated the role of NPM1 in NPC and discovered that NPM1 was elevated in clinical NPC samples and served as a predictor of the worst prognosis in NPC patients. Furthermore, the upregulation of NPM1 promoted the migration and the cancer stemness of NPC both in vitro and in vivo. Mechanistic analyses revealed that the E3 ubiquitin ligase Mdm2 was recruited by NPM1 to induce the ubiquitination-mediated proteasomal degradation of p53. Ultimately, knockdown of NPM1 suppressed the stemness and EMT signals. In summation, this study demonstrated the role and the underlying molecular mechanism of NPM1 in NPC, providing the evidence for the clinical application of NPM1 as a therapeutic target for the treatment of patients with NPC.

• Authors: Liya Hu, Pinggui Gong, Ni Zhou, Shuilian Wang, Cui He, Yixuan Zhou, Qiwen Li, Xueman Zhao, Hong Peng
• Journal: American journal of cancer research (Am J Cancer Res) Vol. 13 Issue 5 Pg. 1766-1785 ( 2023) ISSN: 2156-6976 [Print] United States
• PMID: 37293161 (Publication Type: Journal Article)
• Copyright: AJCR Copyright © 2023.